Oxytricha fallax, a ciliated protozan, has two nuclei in its one cell. The somatic or macronucleus (MA) and the germ-line micronucleus (MI) derive from identical (mitotic) products of the zygotic nucleus following mating. The MA is derived via a massive and complex set of processes which involve specific DNA fragmentation, specific sequence amplification, specific sequence destruction of a fraction of the germ-line sequences, and probably specific sequence rearrangement of the surviving DNA. These dramatic alterations of the to-be-somatic genome yield the MA, which is fully and solely responsible for vegetative growth. In order to study the mechanisms of these genome alterations, we are expanding two approaches previously employed. First, assuming that vegetative MAs and MIs represent the starting material and end product of macronuclear development in the sexual stage, we shall study the ultimate fates of specific (cloned) MI sequences and the contexts of specific MA sequences in the MI DNA to ask such questions as which MI sequences survive to become MA sequences, what distinguishes surviving from non-surviving sequences; what sites of action can be deduced; what is the nature of survivor (and non-survivor) sequence rearrangements; in what context lie the MI sequences which come to make up specific MA sequence blocks? Second, the MA development process will be studied directly, using cytogenetics and modern DNA biochemistry (again, genetic engineering, DNA-cloning, etc.), and detection and isolation of site-specific proteins involved.